For the past decade, the University of Wisconsin Biotechnology Center DNA Sequencing Facility has met the sequencing needs of over 150 NIH-funded laboratories at UW-Madison using Sanger dideoxy automated sequencers. In this proposal, funds are requested to purchase the University of Wisconsin's first 'next generation'DNA sequencer, an Illumina Genome Analysis System, that will be operated by this core facility. Our goal is to provide ready, cost-effective access to this relatively new technological platform to all NIH-funded researchers at UW- Madison. This instrument currently produces a gigabase of sequence derived from millions of short sequence reads, of ca. 30-50bp, in ca. 3 days, for less than $10,000 in consumable reagents. Because of these short sequences, the requested instrument is to be used primarily for experiments with RNA or DNA derived from organisms for which a pre-existing good quality genome sequence exists. Many NIH- funded researchers at UW-Madison work with model organisms whose genomes have been sequenced, such as E. coli, yeast, C. elegans, Drosophila, mice and rats. Thus, this technology platform is particularly applicable to their research needs. The use of next-generation sequencers continues to escalate and various innovations are allowing them to become more flexible and applicable to routine experiments. Ready access to this technology platform will accelerate both the pace and scope of basic medical research at UW-Madison. This past year, the NIH invested ca. $250 million in research projects led by investigators at UW-Madison, some of which are significantly disadvantaged by the absence of high-throughput sequencing capability. In this proposal, we will highlight nine laboratories out of many funded by NIH that have specific, immediate and critical needs best met by providing high-throughput, next-generation capabilities on campus. The broad range of research projects described along with the impact that this technology will have on the research programs clearly demonstrates the mission-critical need to acquire this instrument to support NIH's research portfolio at UW. Placing this high-end instrumentation in a core facility will provide local cost-effective access to this technological platform and also will ensure that the instrument is heavily used and well maintained. Local access also will help in the adoption of this new genomic tool by investigators currently unfamiliar with the technology and capabilities of this instrument. PUBLIC HEALTH RELEVANCE: There is no better storehouse of information about a living species than the information encoded in its genome. Determining the complete genomic sequence of a species provides only a limited view of the available information. The variation present in each species, readily accessible via new sequencing technologies, provides the key to new advances in evolutionary biology, pathogen evolution, cancer biology, personalized medicine, and in developing the next generation of cures for human disease.